1. Field of the Invention
The field of this invention concerns cosmetic compositions, particularly skin care related to skin hormonal imbalance.
2. Related Art
Mammalian skin and associated characteristics, such as wrinkles and hair growth and loss, are significantly affected by hormones, and the individual skin responsiveness to their levels and ratios, since there is substantial interest in the treatment of skin and its associated characteristics, there have been numerous reports of treatment as palliatives and cures.
1. Wrinkle Reduction:
Wrinkles are skin folds and creases caused by dermal thinning and loss of elasticity, which is a result of the aging process and/or exposure to noxious substances and/or physical factors such as UV radiation, all of which adversely affect the skin metabolism. Wrinkles are not a medical condition and as long as the substances employed to treat them are not systemically resorbed and systemically active, the preparations fall into the field of cosmetics.
There are many claims to inventions for non-surgical wrinkle reduction or removal, but there are few systematic studies to support such claims. There is a plethora of facial creams available containing a variety of substances, many of which are either inefficient or induce side effects at the levels of efficacy. Thus, it is known that topical vitamin C, tretinoin, or isotretinoin, while transiently improving the wrinkles caused by aging and photo damage, have a considerable incidence of irritation. Inducing paresis of the muscle fibers for cosmetic purposes by substances blocking the neuromuscular junctions is not physiologically acceptable and has its own particular toxicity.
Topical and/or systemic application of estrogens of human origin have been shown to increase the skin collagen content and thus increase skin thickness as well as the concentration of skin mucopolysaccharides, which directly reduces the wrinkles' depth. However, giving mammalian estrogens systemically for the sole purpose of reducing the signs of skin aging would not be medically defensible. Dermatologists have explored topical estriol and 17-β-estradiol and found reduction in the wrinkle depth and increased hydration, but also, albeit to a degree, a systemic resorption resulting in a rise in prolactin (Schmidt et al., 1996 Int J Dermatol 35(9):669-74). Therefore, topical mammalian estrogens for skin regeneration, although effective, cannot qualify as a cosmetic preparation and are not authorized in cosmetic creams. Certain phytoestrogens, especially the isoflavones, which are found in a variety of plants, as are the flavonoids, were shown to have a much lower effect than the mammal estrogens. However, in a topical application they are not resorbed systemically (Bayerl and Keil, 2002 Akt Dermatol 28:14-8).
There are many combinations of different ingredients in cosmetics, such as antioxidants, enzymes, phytoestrogens, emollients, humectants, and the like. Their ability to protect the skin and reduce the formation of wrinkles varies with the composition and its ingredients.
There is, therefore, a need for a safe, effective cosmetic that reduces wrinkling, has minimal or no side effects, such as erythema, edema or irritation, is not systemically resorbed when applied to the skin and does not result in a change in the skin coloration, e.g., is substantially transparent when applied.
2. Compositions Affecting Female Facial Hair Growth (Idiopathic Hirsutism):
Approximately eight percent of women are affected by idiopathic hirsutism (IH), i.e., excessive male-like pattern hair growth without underlying systemic endocrine pathology. IH is characterized either by higher sensitivity of the hair follicle androgen receptors to the androgens or by higher skin androgen levels. IH is considered a skin hyperandrogenetic syndrome in the cosmetic category since especially dark excessive facial hair is visible and leads to psychological distress.
The current treatment is topical and/or systemic pharmacological, combined with mechanical removal including shaving, depilatories, waxing, plucking, laser, intense pulsed light, and/or electrolysis. Metformin, primarily an antidiabetic treatment, known to be often associated with adverse gastrointestinal effects, is indicated only when IH is concomitant.
The androgen-targeting drugs improve female IH either by suppression of the male hormone synthesis such as by inhibiting 5-α reductase conversion of testosterone to dihydrotestosterone (by finasteride), or by blocking the androgen receptors. Finasteride and antiandrogens are contra-indicated in women of childbearing age as they can cause feminization of the male fetus. Cyproterone acetate (CPA), a progestagen with anti-androgenic properties, carries the risk of hypertension, thromboembolism, diabetes mellitus, hypercholesterolemia and endometrial cancer. An antiandrogen of steroidal structure for topical use was recently published (see Labrie et al.). Non-steroidal blocking agents of the androgen receptor, such as flutamide or bicalutamide, prevent the androgen binding. When tested topically in male androgenetic alopecia they proved to be substantially systemically resorbed; they are not approved for IH therapy. The antiandrogens, RU 58841 and RU 56187, i.e., N-substituted aryl hydantoins or thiohydantoins were tested topically; they are nevertheless converted systemically into a common metabolite, which is strongly antiandrogenic. Topical eflornithine inhibits ornithine decarboxylase and thus the conversion of ornithine to putrescine, which regulate the anagen phase of the hair growth.
Mechanical depilation by tweezing and depilatory can potentially exacerbate IH by stimulating the growth of thicker and coarser hair, making subsequent treatments more difficult and occasionally inducing folliculitis and trauma to the hair shaft and skin.
IH can be considered a medical condition, but as long as the substances employed to treat IH are not dermally resorbed into the body to become systemically active, the preparations fall into the field of cosmetics. A topical cosmetic composition not resorbed systemically, reducing the hair diameter, color and rate of growth and not changing the appearance of the skin would be of benefit to women affected by unwanted body hair.
Relevant Literature
For wrinkles, the use of natural extracts and their fractions has found extensive use in cosmetics: resveratrol, WO04/026,222, WO01/30314; Glycine soja, U.S. patent application nos. 2004/0191350, 2005/0048105, 2005/0112153; grape seed oil, WO01/17495; Boswellia serrata, U.S. patent application no. 2005/01213559 and WO00/0578393; and Cocos nucifera, U.S. Pat. No. 6,551,656. Fluridil has been previously employed in formulations useful in a variety of conditions where its effect on the skin receptors is desirable (U.S. Pat. No. 6,184,249, which is specifically incorporated by reference herein, Sovak et al., 2001 WO 01/58854; 2002 Dermatol Surg 28:678-85; Seligson et al., 2003 Drug Dev Res 59:292-306).
Relevant Literature
References of interest for treating wrinkles include U.S. Pat. Nos. 5,889,054, 6,139,829, and 1,180,133. A discussion of hormone replacement is found in Sator et al., 2004 Exp Dermatol 13 Suppl 4:36-40.
For IH, see Goodheart H., “Hirsutism: Pathogenesis and Causes,” Women's Health Prim Care 2000, 3:329-37; Azziz R., “The evaluation and management of hirsutism,” Obstet Gynecol 2003, 101:995-1007; Shenenberger D, Utecht L., “Removal of unwanted facial hair,” Am Fam Physician 2002, 66:1907-11; and Dawber R P. “Guidance for the management of hirsutism,” Current Medical Research and Opinion, 2005, 21:1227-1234(8). Also, D. Cousty-Berlin et al., “Preliminary Pharmacokinetics and Metabolism of Novel Non-steroidal Antiandrogens in the Rat: Relation of their Systemic Activity to the Formation of a Common Metabolite,” Steroid Biochem Molec Biol 1994, 51:47-55, and Labrie et al., “Topical antiandrogenic steroids,” US 2004/0224935, Nov. 11, 2004.